title: Lysophosphatidic acid induces shear stress-dependent contraction in mouse aortic strip in situ.
abstract: We previously reported that lysophosphatidic acid (LPA) regulates Ca²⁺ influx of fluid flow in stimulated endothelial cells and that LPA and shear stress showed increment and suppressive effects on phenylephrine-induced vasoconstriction and acetylcholine-induced vasodilatation, respectively. However, a vasoconstrictive effect of LPA alone in the presence of shear stress was not found. The present study examined the effect of LPA alone in the presence of shear stress on Ca²⁺ responses in endothelial and smooth muscle cells and contraction in mouse aortic strip using real-time 2-photon laser scanning microscopy and a custom-made parallel-plate flow chamber. Application of micromolar LPA and high shear stress elicited movement of endothelial cells after Ca²⁺ responses. The endothelial cells moved along the major axis of smooth muscle cells, a direction that was identical to that found during vasoconstriction evoked by the application of phenylephrine. The frequency of Ca²⁺ oscillations in smooth muscle cells was highest according to endothelial movement. Vasoconstriction evoked by LPA and shear stress was significantly reduced by the application of a thromboxane A₂ receptor antagonist, a cyclooxygenase inhibitor, and a thromboxane synthase inhibitor. These results suggest that micromolar LPA and high shear stress elicit vasoconstriction that is caused by Ca²⁺-dependent contraction in medial smooth muscle cells. Thromboxane A₂ may be involved in that response.
authors.affiliation: *Center for Development in Higher Education, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan; and †Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
authors.forename: Takeharu
authors.initials: T
authors.lastname: Niioka
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Ohata
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Momose
authors.forename: Kazuo
authors.initials: K
authors.lastname: Honda
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008246:Lysophospholipids / Q000378:metabolism*; D008297:Male; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D033081:Shear Strength; D013312:Stress, Physiological / Q000187:drug effects; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase; C032881:lysophosphatidic acid